tailieunhanh - The signals of FGFs on the neurogenesis of embryonic stem cells

Neural induction is a complex process and the detailed mechanism of FGF-induced neurogenesis remains unclear. Methods: By using a serum-free neural induction method, we showed that FGF1 dose-dependently promoted the induction of Sox1/N-cadherin/nestin triple positive cells, which represent primitive neuroblasts, from mouse embryonic stem (ES) cells. Results: We demonstrated that FGF1, FGF2, and FGF4, but not FGF8b, enhanced this neurogenesis. Especially, FGFenhanced neurogenesis is not mediated through the rescue of the apoptosis or the enhancement of the proliferation of Sox1+ cells. We further indicated that the inactivation of c-Jun. | Chen et al. Journal of Biomedical Science 2010 17 33 http content 17 1 33 a NSC Tha cost of publication In Journal of Blomodlcal Science Is bome by tlM National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access The signals of FGFs on the neurogenesis of embryonic stem cells Ching-Wen Chen 1 Chin-San Liu2 Ing-Ming Chiu3 Shih-Cheng Shen1 Hung-Chuan Pan4 Kun-Hsiung Lee5 Shinn- Zong Lin6 and Hong-Lin Su 1 7 Abstract Background Neural induction is a complex process and the detailed mechanism of FGF-induced neurogenesis remains unclear. Methods By using a serum-free neural induction method we showed that FGF1 dose-dependently promoted the induction of Sox1 N-cadherin nestin triple positive cells which represent primitive neuroblasts from mouse embryonic stem ES cells. Results We demonstrated that FGF1 FGF2 and FGF4 but not FGF8b enhanced this neurogenesis. Especially FGF-enhanced neurogenesis is not mediated through the rescue of the apoptosis or the enhancement of the proliferation of Sox1 cells. We further indicated that the inactivation of c-Jun N-terminal kinase-1 JNK-1 and extracellular signal-related kinase-2 ERK-2 but not p38 mitogen-activated protein kinase MAPK inhibited the neural formation through the inhibition of ES differentiation but not through the formation of endomesodermal cells. Conclusions These lines of evidence delineated the roles of FGF downstream signals in the early neural differentiation of ES cells. Background In the early gastrula of the chicken temporary treatment of the primitive ectoderm with Hensen s node for 5 hours steers the ectoderm to become the neural fate 1 2 . FGF was shown to be responsible for this instructive ability of node and for the maintenance of later neural instructive signals 3 4 . FGF first activates ERNI during early gastru-lation and consequently triggers the zinc-finger transcriptional activator Churchill and its downstream target Sipl in late gastrulation 4 . In Xenopus .